l-Theanine Inhibits (-)-Epigallocatechin-3-gallate Oxidation via Chelating Copper.

Our recent study showed that glutamate can inhibit dopamine oxidation via chelating copper. l-Theanine is an amino acid analogue of glutamate, whereas tea (-)-epigallocatechin-3-gallate (EGCG) is similar to dopamine in avidly undergoing oxidation. We thus hypothesized that l-theanine could also restrain EGCG oxidation via chelating copper. The current study scrutinized influences of l-theanine on EGCG oxidation in vitro and in vivo. The in vitro results showed that l-theanine and copper formed an l-theanine-copper complex with impaired redox activity of copper. Accordingly, l-theanine effectively suppressed copper-facilitated EGCG oxidation, hydroxyl radical production, and DNA damage; inhibited EGCG autoxidation which in essence involves catalysis of transition metals such as copper; and reduced EGCG oxidation-associated formation of a quinone adduct with proteins known as quinoproteins. Consistently, l-theanine significantly increased hepatic EGCG levels and reduced hepatic quinoprotein levels and liver injury in mice treated with EGCG. These lines of evidence together suggest that tea l-theanine can protect against tea catechin oxidation.

Prooxidant activity-based guideline for a beneficial combination of (-)-epigallocatechin-3-gallate and chlorogenic acid.

In the current study, the prooxidant activities of (-)-epigallocatechin-3-gallate (EGCG) and chlorogenic acid (CGA) were systematically compared both in multiple in vitro models and in mice. At equimolar concentrations in vitro and in vivo, EGCG displayed powerful prooxidant effects though CGA exhibited none. In vitro, though CGA and EGCG synergistically produced hydrogen peroxide, CGA was able to scavenge hydroxyl radicals generated by EGCG/copper. Consistent with the selective modulation of reactive oxygen species produced from EGCG, CGA lowered hepatotoxicity but did not perturb hepatic AMPK activation nor the increase of hepatic Nrf2-associated proteins induced by high-dose EGCG. CGA, along with low-dose EGCG, synergistically activated hepatic AMPK and increased hepatic Nrf2-associated proteins without causing toxicity in mice. This proof-of-principle study suggests that polyphenols with potent prooxidant activities (e.g., EGCG) together with antioxidant polyphenols with noticeably low prooxidant activities (e.g., CGA) may yield health benefits with a low risk of side effects.